Pluripotent stem cells, such as embryonic stem cells (ESCs), can self-renew and differentiate into all somatic cell types. Somatic cells have been reprogrammed to become pluripotent via nuclear transfer into oocytes or through the ectopic expression of defined factors (Wilmut, et al., Nature, 385:810-813 (1997); Takahashi, et al., Cell, 126:663-676 (2006); Yamanaka, et al., Nature, 465:704-712 (2010) and Stadtfeld, et al., Genes Dev., 24:2239-2263 (2010)). However, exogenous pluripotency-associated factors, especially Oct4, are indispensable in these methods for establishing pluripotency (Zhu, Annu. Rev. Biomed. Eng., 13:73-90 (2011); Li, Cell Res., 21:196-204 (2011) and Li, et al., Proc. Natl. Acad. Sci. U.S.A., 109:20853-20858 (2012)). Additionally, the requirement for tumorigenic genes like c-Myc in these reprogramming methods creates a risk of inducing cancerous cells. Accordingly, reprogramming strategies have raised concerns regarding the clinical applications (Saha, et al., Cell Stem Cell, 5:584-595 (2009) and Wu, et al., Cell Biol., 13:497-505 (2011)).
There is a need for small molecules which can drive reprogramming of somatic cells into pluripotent cells. Small molecules that can induce pluripotency have advantages because small molecules more readily penetrate the cells, they are nonimmunogenic, more cost-effective, and more easily synthesized, preserved, and standardized.
It is an object of the present invention to provide small molecules which can be used to reprogram partially or completely differentiated cells into pluripotent cells.
It is also an object of the present invention to provide a method of reprogramming partially or completely differentiated cells into pluripotent cells.